Prediabetes is a reversible, intermediate stage of type 2 diabetes mellitus (T2DM). Lifestyle changes that include healthy diet and exercise can substantially reduce progression to T2DM. The present study explored the association of 37 T2DM- and obesity-linked single nucleotide polymorphisms (SNPs) with prediabetes risk in a homogenous Saudi Arabian population. A total of 1129 Saudi adults [332 with prediabetes (29%) and 797 normoglycemic controls] were randomly selected and genotyped using the KASPar SNP genotyping method. Anthropometric and various serological parameters were measured following standard procedures. Heterozygous GA of HNF4A-rs4812829 (0.64; 95% CI 0.47-0.86; p < 0.01), heterozygous TC of WFS1-rs1801214 (0.60; 95% confidence interval (CI) 0.44-0.80; p < 0.01), heterozygous GA of DUSP9-rs5945326 (0.60; 95% CI 0.39-0.92; p = 0.01), heterozygous GA of ZFAND6-rs11634397 (0.75; 95% CI 0.56-1.01; p = 0.05), and homozygous AA of FTO-rs11642841 (1.50; 95% CI 0.8-1.45; p = 0.03) were significantly associated with prediabetes, independent of age and body mass index (BMI). Additionally, C-reactive protein (CRP) levels in rs11634397 (AA) with a median of 5389.0 (2767.4-7412.8) were significantly higher than in the heterozygous GA genotype with a median of 1736.3 (1024.4-4452.0) (p < 0.01). In conclusion, only five of the 37 genetic variants previously linked to T2DM and obesity in the Saudi Arabian population [HNF4A-rs4812829, WFS1-rs1801214, DUSP9-rs5945326, ZFAND6-rs11634397, FTO-rs11642841] were associated with prediabetes susceptibility. Prospective studies are needed to confirm the potential clinical value of the studied genetic variants of interest.
Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population
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